基于有氧糖酵解的天然小分子抑制剂的研究进展

Research progress of natural small molecule inhibitors based on aerobic glycolysis

有氧糖酵解作为恶性肿瘤最显著的能量代谢特征之一,肿瘤细胞中大约有50%的ATP是通过有氧糖酵解途径合成的,同时糖酵解过程中产生的各种中间代谢产物也是合成蛋白质等生物大分子重要的原料来源。此外酵解途径导致的乳酸增加为肿瘤细胞提供了一个酸性成长环境,有利于其浸润和转移,因此其在维持肿瘤细胞能量需求、合成代谢平衡和肿瘤浸润和转移方面发挥着重要作用。研究表明有氧糖酵解的过程与葡萄糖转运蛋白、己糖激酶、丙酮酸激酶、磷酸果糖激酶等密切相关。目前靶向有氧糖酵解相关转运蛋白和关键限速酶已经成为抗肿瘤药物研发的有效途径,本文对目前天然产物中靶向有氧糖酵解相关蛋白的小分子抑制剂研究最新进展及作用机理进行总结,以期为相关领域药物研究人员提供新的思路和参考。

Aerobic glycolysis is the most prominent feature of energy metabolism in malignant tumors.About 50%of ATP in tumor cells was synthesized through aerobic glycolysis.At the same time,various intermediate metabolites produced in the process of glycolysis were also important raw materials for the synthesis of proteins and other biological macromolecules.In addition,the increase of lactic acid caused by glycolysis pathway could provide an acidic growth environment for tumor cells,which was conducive to their infiltration and metastasis.Therefore,it played an important role in maintaining the energy demand of tumor cells,the balance of anabolism and tumor invasion and metastasis.Studies have shown that the process of aerobic glycolysis was closely related to glucose transporter,hexokinase,pyruvate kinase and phosphofructokinase.At present,targeting aerobic glycolysis-related transporters and key rate-limiting enzymes have become an effective way for the development of antineoplastic drugs.This paper summarizes the latest progress and mechanism of action of small molecule inhibitors targeting aerobic glycolysis-related proteins in natural products,with a view to providing new ideas and references for drug researchers in related fields.